Dynamic protein structures in normal function and pathologic misfolding in systemic amyloidosis.

ABSTRACT: Dynamic and disordered regions in native proteins are often critical for their function, particularly in ligand binding and signaling. In certain proteins, however, such regions can contribute to misfolding and pathologic deposition as amyloid fibrils in vivo. For example, dynamic and disordered regions can promote amyloid formation by destabilizing the native structure, by directly triggering the aggregation, by promoting protein condensation, or by acting as sites of early proteolytic cleavage that favor a release of aggregation-prone fragments or facilitate fibril maturation. At the same time, enhanced dynamics in the native protein state accelerates proteolytic degradation that counteracts amyloid accumulation in vivo. Therefore, the functional need for dynamic protein regions must be

SUBMITTER: Lewkowicz E 

PROVIDER: S-EPMC9416430 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature